Understanding and manipulation of cell-substrate interactions have increased in importance as research in implantable biomaterial advances. One area of interest relates to production of a more natural-like construct that is able to recruit and control patterning of functional cells to mimic natural tissue organization.
Aligned orientation of cells on extracellular matrix (ECM), for example, plays an important role in tissues such as corneal stroma, tendons, bones, skeletal muscle and vasculature.
In particular, development of small diameter vascular prostheses for arterial disease remains problematic due to poor compliance and vasoactivity for small diameter prostheses. For example, the implanted prostheses tend to occlude fairly quickly, compared to saphenous vein grafts. As such, smaller arteries (2 mm to 5 mm) are currently only treated with angioplasty and/or stenting. Other reasons for failure of small blood vessel prostheses in vivo include: (i) compliance mismatch between prosthesis and blood vessel, which leads to anastomic hyperplasia; and (ii) acute and delayed thrombosis due to material used.
Use of two predominant cell types within blood vessels, namely fibroblasts and vascular smooth muscle cells (VSMCs), may functionally benefit cell-seeded prosthesis if they are used in an aligned orientation.
Fibroblasts produce extracellular matrix (ECM) such as collagen fibrils and elastin that confer blood vessels much of their mechanical and structural properties. In the context of a vascular prosthesis, it is beneficial to align growth of cells, as they may in turn control pattern of ECM deposition. As such ECM may gradually replace medical prosthesis constructs formed of a biodegradable material, distribution of the cells and methods of influencing their growth are of importance.
VSMCs represent another predominant cell type within blood vessels. They are integral to vascular functioning through regulation of vessel tone and lumen diameter. Interestingly, these cells exist as two very distinct phenotypes: (i) contractile VSMCs, characterized by their spindle shapes and abundance of alpha smooth muscle actin (α-SMA); and (ii) synthetic VSMCs, recognizable by their rhomboid shapes and reduced α-SMA.
Contractile VSMCs allow changes that mediate blood pressure by altering vessels luminal diameter. Secretary phenotypes, on the other hand, are associated with tissue remodeling, inflammation and proliferation, and are central to pathology of neointimal hyperplasia and artery bypass failure.
There is plasticity between the contractile and phenotype states as they are not differentiation end-points. During culturing of VSMCs, freshly seeded cells exist primarily in the contractile state. Over time, the population shifts towards predominantly secretory phenotypes. Aligned orientation of VSMCs within engineered parallel grooves, however, has been found to preserve the contractile state over extended periods of culturing. Preservation of phenotype is important, as only VSMCs in the contractile state are beneficial in fabricating cellularised tissue engineered blood vessel (TEBV). Furthermore, the cells must be circumferentially orientated to direct their function.
To date, no tissue-engineered construct or fully-synthetic vascular prosthesis has been approved for use in small-diameter blood vessel replacement.
Apart from the above-mentioned, mesenchymal stem cells may be a potential cell source in cardiac regeneration for use in necrotic areas of heart tissue. The mesenchymal stem cells may differentiate towards the cardiomyocyte lineage to restore tissue function. Stem cells may be expanded and cultured ex vivo, whereas cardiomyocytes are terminally differentiated. The concept has been expanded to creating a heart patch scaffold colonized with functioning myocytes for the replacement of infracted heart tissue. The differentiation of mesenchymal stem cell towards cardiomyocytes may be aided by surface cues incorporated into the scaffold. In particular, linear patterning using fibers and cut grooves may promote differentiation of mesenchymal stem cells to cardiomyocytes.
In view of the above, there remains a need for a method to fabricate a patterned surface for cell growth, including implants having such a patterned surface, that overcomes or at least alleviates one or more of the above-mentioned problems.